PROJECT SUMMARY/ABSTRACT Premenstrual Syndrome (PMS) is a psychiatric condition affecting approximately 20% of reproductive-aged women. Despite its high prevalence, very little is known about its etiology. We have designed a future study to show that variation in the reproductive hormone kinetics across the menstrual cycle leads to PMS and to clarify multi-domain pathways of this relationship. The model of this study includes an acute psychosocial stress reactivity component. Therefore, the proposed study will clarify the time within the menstrual cycle at which stress reactivity differs between women with PMS diagnosis and healthy controls. We hypothesize a blunted cortisol response in women with PMS diagnosis upon acute stress challenge during the late luteal phase of the menstrual cycle. Results of this research will advance our understanding of the physiological and psychological milieu which sensitizes susceptible women to be especially vulnerable to stress prior to menstruation. The proposed study will enroll one hundred and twenty healthy women with regular menstrual cycles. They will chart their symptoms, menstruation timing and ovulation for two menstrual cycles. This data will form the basis for PMS diagnosis and predictable bounds of menstrual cycle phases. In the third menstrual cycle, study participants will complete the Trier Social Stress Test session in the late luteal phase of the menstrual cycle. The hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis, cardiovascular system and affective state will be evaluated at baseline and at seven time points following the stress procedure. Knowledge gained from this experiment will increase our understanding of acute stress reactivity specific to the study population, as well as collect key data for our long-term program of research, designed to reduce clinical heterogeneity in PMS.